ADCY7_BOVIN
ID ADCY7_BOVIN Reviewed; 1078 AA.
AC Q29450; O02856;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Adenylate cyclase type 7 {ECO:0000250|UniProtKB:P51828};
DE EC=4.6.1.1;
DE AltName: Full=ATP pyrophosphate-lyase 7;
DE AltName: Full=Adenylate cyclase type VII;
DE AltName: Full=Adenylyl cyclase 7;
GN Name=ADCY7 {ECO:0000250|UniProtKB:P51828};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retina;
RX PubMed=8557110; DOI=10.1016/0014-5793(95)01470-5;
RA Voelkel H., Beitz E., Klumpp S., Schultz J.E.;
RT "Cloning and expression of a bovine adenylyl cyclase type VII specific to
RT the retinal pigment epithelium.";
RL FEBS Lett. 378:245-249(1996).
CC -!- FUNCTION: Catalyzes the formation of cAMP in response to activation of
CC G protein-coupled receptors. Functions in signaling cascades activated
CC namely by thrombin and sphingosine 1-phosphate and mediates regulation
CC of cAMP synthesis through synergistic action of the stimulatory G alpha
CC protein with GNA13 (By similarity). Also, during inflammation, mediates
CC zymosan-induced increase intracellular cAMP, leading to protein kinase
CC A pathway activation in order to modulate innate immune responses
CC through heterotrimeric G proteins G(12/13) (By similarity). Functions
CC in signaling cascades activated namely by dopamine and C5 alpha chain
CC and mediates regulation of cAMP synthesis through synergistic action of
CC the stimulatory G protein with G beta:gamma complex (By similarity).
CC Functions, through cAMP response regulation, to keep inflammation under
CC control during bacterial infection by sensing the presence of serum
CC factors, such as the bioactive lysophospholipid (LPA) that regulate
CC LPS-induced TNF-alpha production. However, it is also required for the
CC optimal functions of B and T cells during adaptive immune responses by
CC regulating cAMP synthesis in both B and T cells (By similarity).
CC {ECO:0000250|UniProtKB:P51828, ECO:0000250|UniProtKB:P51829}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP = 3',5'-cyclic AMP + diphosphate; Xref=Rhea:RHEA:15389,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:58165; EC=4.6.1.1;
CC Evidence={ECO:0000250|UniProtKB:P51828};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P30803};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P30803};
CC Note=Binds 2 magnesium ions per subunit. Is also active with manganese
CC (in vitro). {ECO:0000250|UniProtKB:P30803};
CC -!- ACTIVITY REGULATION: Activated by the G protein alpha subunit.
CC Activated by the G protein beta and gamma subunit complex. Activated by
CC GNA13 and GNA12. Ethanol and phorbol 12,13-dibutanoate significantly
CC potentiate adenylate cyclase activity generated in response to the
CC activation of the prostanoid receptor by the agonist prostaglandin
CC E1(1-) in a PKC-dependent manner (By similarity). Inhibited by lithium
CC (By similarity). {ECO:0000250|UniProtKB:P51828,
CC ECO:0000250|UniProtKB:P51829}.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Found exclusively in the retinal pigment
CC epithelium.
CC -!- DOMAIN: The protein contains two modules with six transmembrane helices
CC each; both are required for catalytic activity. Isolated N-terminal or
CC C-terminal guanylate cyclase domains have no catalytic activity, but
CC when they are brought together, enzyme activity is restored. The active
CC site is at the interface of the two domains. Both contribute substrate-
CC binding residues, but the catalytic metal ions are bound exclusively
CC via the N-terminal guanylate cyclase domain.
CC {ECO:0000250|UniProtKB:P26769}.
CC -!- PTM: Phosphorylated by PRKCD. {ECO:0000250|UniProtKB:P51828}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA89894.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; Z49806; CAA89894.1; ALT_INIT; mRNA.
DR RefSeq; NP_776655.1; NM_174230.2.
DR RefSeq; XP_005218501.1; XM_005218444.3.
DR AlphaFoldDB; Q29450; -.
DR SMR; Q29450; -.
DR STRING; 9913.ENSBTAP00000008153; -.
DR PaxDb; Q29450; -.
DR GeneID; 281603; -.
DR KEGG; bta:281603; -.
DR CTD; 113; -.
DR eggNOG; KOG3619; Eukaryota.
DR HOGENOM; CLU_001072_2_5_1; -.
DR InParanoid; Q29450; -.
DR OrthoDB; 363718at2759; -.
DR TreeFam; TF313845; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004016; F:adenylate cyclase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0006171; P:cAMP biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0071361; P:cellular response to ethanol; ISS:UniProtKB.
DR GO; GO:0071285; P:cellular response to lithium ion; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; ISS:UniProtKB.
DR GO; GO:0002819; P:regulation of adaptive immune response; ISS:UniProtKB.
DR CDD; cd07302; CHD; 2.
DR Gene3D; 3.30.70.1230; -; 2.
DR InterPro; IPR001054; A/G_cyclase.
DR InterPro; IPR018297; A/G_cyclase_CS.
DR InterPro; IPR032628; AC_N.
DR InterPro; IPR030672; Adcy.
DR InterPro; IPR009398; Adcy_conserved_dom.
DR InterPro; IPR029787; Nucleotide_cyclase.
DR Pfam; PF16214; AC_N; 1.
DR Pfam; PF06327; DUF1053; 1.
DR Pfam; PF00211; Guanylate_cyc; 2.
DR PIRSF; PIRSF039050; Ade_cyc; 1.
DR SMART; SM00044; CYCc; 2.
DR SUPFAM; SSF55073; SSF55073; 2.
DR PROSITE; PS00452; GUANYLATE_CYCLASE_1; 1.
DR PROSITE; PS50125; GUANYLATE_CYCLASE_2; 2.
PE 2: Evidence at transcript level;
KW ATP-binding; cAMP biosynthesis; Glycoprotein; Lyase; Magnesium; Manganese;
KW Membrane; Metal-binding; Nucleotide-binding; Reference proteome; Repeat;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..1078
FT /note="Adenylate cyclase type 7"
FT /id="PRO_0000195702"
FT TOPO_DOM 1..33
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 34..54
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 63..83
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 95..120
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 125..145
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 150..170
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 176..196
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 197..594
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 595..615
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 620..640
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 669..688
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 718..737
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 746..773
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 792..812
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 813..1078
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 455..476
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 477..482
FT /note="Mediates regulation of adenylate cyclase activity by
FT C5 alpha-induced G- beta and gamma pathway"
FT /evidence="ECO:0000250|UniProtKB:P51828"
FT REGION 491..499
FT /note="Mediates regulation of adenylate cyclase activity by
FT sphingosine 1-phosphate-induced G alpha 13 pathway"
FT /evidence="ECO:0000250|UniProtKB:P51828"
FT REGION 502..545
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 506..584
FT /note="Modulates adenylate cyclase activity by modulating
FT the binding of G(s)alpha to the high-affinity G(s)alpha
FT binding site in 7C1a/7C2"
FT /evidence="ECO:0000250|UniProtKB:P51828"
FT COMPBIAS 455..475
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 526..545
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 284..289
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 284
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 284
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 285
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 326..328
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 328
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 328
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 372
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 929
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1008..1010
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1015..1019
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1055
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT CARBOHYD 701
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 776
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 781
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1078 AA; 120820 MW; 50E89BF08E37FCBB CRC64;
MPAKGRYFLN EGEEGPDQDA LYEKYRLTSQ HGPLLLMLLL VAIAACTTLI VITFSYGDPS
RHRAVLGTAF FTLAMFVLLY ALVYVECLDR RGLRISALLI WGCLVTLGYV LVFDFDSPRK
DTLCLWGRCP SSSFVVFVVY TLLPFSMWGA VTAGLVSSIS HLLVLAMHQE DFTSPVGLKL
LATAVVFVCG NLTGAFHKHH MQDASHDLFT YTVKCIQIRR KLRIEKRQQE NLLLSVLPAH
ISMGMKLAII ERLKERGDRR YLPDNNFHNL YVKRHQNVSI LYADIVGFTR LASDCSPKEL
VVVLNELFGK FDQIAKANEC MRIKILGDCY YCVSGLPVSL PNHARNCVKM GLDMCEAIKQ
VREATGVDIS MRVGIHSGNV LCGVIGLRKW QYDVWSHDVS LANRMEAAGV PGRVHITEAT
LKHLDKAYEV EDGHGQQRDP YLKEMNIRTY LVIDPRSQQP PQPSQHNSKN KGNATLKMRA
SVRMTRYLES WGAARPFAHL NQRESVSSSE TLVSHGRRPK AVPLRRHRTP DRSASPKGRS
EDDSYDDEML SAIEGLSSTR PCCSKSDDFS TFGSIFLEKG FEREYRLAPI PRVRYYFACA
SLVFVCILLI HVLLLYSMKT LGVSFGLVAC VLGLVLGLCF ADVFLRCCPA LGKLRAIAES
VETQPLLRVS LAILTIGSLL VIAVVNLPLM PFRDRGLTAG NETGLRAVSG WEMSPCYLLP
YYTCSCILAF IACSVFLRMS LELKVVLLTV ALVAYLVLFN VYPSWQWDCC GHSLGNLTGT
NGTLSSSSCS WHLKTMTNFY LVLFYTTLIM LSRQIDYYCR LDCLWKKKFK KEHEEFETME
NVNRLLLENV LPAHVAAHFI GDKLNEDWYH QSYDCVCVMF ASVPDFKVFY TECDVNKEGL
ECLRLLNEII ADFDELLLKP KFSGVEKIKT IGSTYMAAAG LSVPSGPENQ DLERQHAHIG
IMVEFSTALM SKLDGINRHS FNSFRLRVGI NHGPVIAGVI GARKPQYDIW GNTVNVASRM
ESTGELGKIQ VTEETCTILQ GLGYSCECRG LIDVKGKGEL RTYFVCTDTA KFQGLGLN
